Macrophage differentiation and functional polarization: role of thyroid hormones

Abstract

Macrophages can be divided on basis of their function: classically activated macrophages (often referred to as M1) and alternatively activated macrophages (typically named M2). There is evidence that different endocrine stimuli influence macrophages differentiation with a mosaic of different and overlapping characteristics. In this study, we verified for the first time the role of thyroid hormone (TH) system on macrophage differentiation/polarization through in vitro and in vivo approaches. Monocites were isolated from femur bone marrow derived cells and primary cultures of differentiated macrophages (MΦ) were obtained. MΦ were also polarized to generate M1 and M2 subtypes. In these cells, we demonstrated different levels of TH receptors (TRalfa1, TRbeta1, and TRbeta2). Cells were then treated with TH during MΦ differentiation, as well as during polarization to M1 or M2, and the hormone‐induced effects were determined. For instance, a set of specific cell‐surface molecules and cytokine/receptor genes were measured. In addition, we determined TH effects on cell proliferation, cell viability, phagocytosis, nitric oxide synthase and arginase protein expression, cytokine release, and cell migration. In vivo experiments were also conducted in euthyroid and hypothyroid mice. In particular, we analysed the animal survival rate and the presence of cell‐surface molecules in peritoneal macrophages of mice both in control conditions and during systemic inflammation. Taken toghether, our data suggest that TH has a role in modulating specific properties of macrophage populations and the functional balance M1/M2.